July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Thermo-sensitive hydrogel for the controlled release of Aflibercept: in vitro release and ex vivo bioactivity
Author Affiliations & Notes
  • Xinxin Zhao
    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
  • Kun Xue
    IMRE, Singapore
  • Xinyi Su
    Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
  • Footnotes
    Commercial Relationships   Xinxin Zhao, None; Kun Xue, None; Xinyi Su, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 137. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Xinxin Zhao, Kun Xue, Xinyi Su; Thermo-sensitive hydrogel for the controlled release of Aflibercept: in vitro release and ex vivo bioactivity. Invest. Ophthalmol. Vis. Sci. 2019;60(9):137.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose :
Intravitreal injections of anti-VEGFs are used as the first line for neovascularization, but concomitant with invasive repeated injections induced complications. We report a 50 days in vitro sustained release of anti-VEGFs, using an injectable thermo-sensitive hydrogel composed by tri-blocked copolymer of PEG, PPG and PCl.

Methods : In vitro release of Anti-VEGFs: Avastin at 2.5 wt% and 1 wt%; Eylea at 4 wt% and 1 wt% were added into hydrogel foam and incubate at 4 °C. Until the gel formation, PBS was added at 37 °C to initiate the release with shaking at 50 rpm. Half volume of PBS will be collected at certain intervals for protein quantification and further bioactivity test.
Ex vivo bioactivity test of anti-VEGF incorporated hydrogel: Mice choroid explant was used and cultured with & without of anti-VEGF incorporated hydrogel

Results : A sustained in vitro release of Avastin (39 days) and Eylea (46 days) was achieved by adopting 20 wt% thermo-sensitive triblocks poly(PEG-PPG-PCl) hydrogel. An Anti-VEGFs concentration-related release profile was observed, that at higher concentration (2.5 wt% of Avastin & 4 wt% of Eylea) by using the protein stock solution directly, faster and inhomogeneous, drug-diffusion dominated released was obtained. However, at lower protein concentration at 1 wt%, hydrogel erosion dominated protein release was found. The bioactivity of the released anti-VEGFs was evaluated by ELISA and ex vivo assay. By using co-incubation with mice choroidal explants, anti-VEGFs loaded hydrogel showed significant anti-angiogenitic effect by inhibition the vessel expansion of the explants, suggesting the bioactivity of the anti-VEGFs loaded within hydrogel. The long term bioactivity of the released VEGFs from hydrogel was examined by ELISA assay. About 40% of bioactivity was observed after 21 days release.

Conclusions :
A novel 20 % wt/v thermo-sensitive hydrogel was used for sustained release of Avastin and Eylea, about 39 days and 46 days sustained release, respectively was achieved in vitro. The bioactivity of the hydrogel loaded Avastin and Eylea was proved by an ex vivo mice choroidal explant assay, which was further proved by an ELISA kit that about 40% bioactivity was preserved after 21 days release.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Eylea encapsulated hydrogel release profile

Eylea encapsulated hydrogel release profile

 

Bioactivity test of anti-VEGFs loaded inside the hydrogel by ex vivo mice choroidal explant assay

Bioactivity test of anti-VEGFs loaded inside the hydrogel by ex vivo mice choroidal explant assay

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×